1. Field of the Invention
The present invention relates generally to the use of γ-glutamyl antioxidants, particularly γ-glutamyl -cysteine, as cytoprotective agents to prevent reperfusion injury (i.e., hemorrhagic transformation) of the blood-brain barrier during reperfusion following an ischemic stroke. The γ-glutamyl antioxidants can be used alone or used in combination with an agent which inhibits the reverse movement of Na/Ca exchange in the blood-brain barrier such as 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate (KB-R7943).
2. Background of the Invention
In the United States, someone experiences a stroke every minute, and dies from stroke-related complications approximately every three minutes. Strokes may be ischemic or hemorrhagic, but most are due to interrupted blood flow to the brain, resulting in hypoxia. Thus, the treatment for cerebral ischemia accompanying stroke includes therapies to re-establish blood flow. Surprisingly, reperfusion following cerebral ischemia may cause damage to the blood-brain barrier (Todd N V, Picozzi P, Crockard H A, and Russell R W R. Reperfusion after cerebral ischaemia: influence of duration of ischaemia. Stroke 17: 460-466, 1986) that can precipitate cerebral edema, hemorrhage, and ensuing neuropathologies. Thus, the cure may actually augment the disease. This appears to be especially true if reperfusion is delayed several hours, and current practice is to avoid reperfusing a patient after three hours of ischemia. Recent evidence has verified that using tissue plasminogen activator (t-PA) to dissolve clots is an effective treatment for stroke, if administered within the three hour interval. Unfortunately, statistics reveal that 95% of stroke victims are not treated in time. Thus, it is clear that finding a way to prevent the potential side-effects associated with thrombolysis would be a significant and life-saving contribution. The present invention discloses the use of γ-glutamyl antioxidants, particularly γ-glutamyl-cysteine, to prevent reperfusion injury (i.e., hemorrhagic transformation) of the blood brain barrier during thrombolytic treatment of ischemic stroke. The γ-glutamyl antioxidants can be used alone or used in combination with an agent which inhibits the reverse movement of Na/Ca exchange in the blood-brain barrier such as 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate (KB-R7943).
These and other aspects and attributes of the present invention will be discussed with reference to the following drawings and accompanying specification.